This comparative study found that THPO expression was significantly higher in HCC tissues than in their cirrhotic counterparts, at both the mRNA and protein levels, with THPO-producing malignant hepatocytes mainly localized at stroma contact sites, where THPO target cells, including vascular cell, platelet, and cancer-stem-cell niches, might potentially create a microenvironment conductive to tumorigenesis, angiogenesis, and metastatic spread. Here, THPO is linked to hepatocellular carcinoma.